- Email: [email protected]
Chinese action towards global malaria eradication – Authors' reply
Correspondence
To coincide with World Malaria Day, The Lancet published a Review by Gretchen Newby and colleagues (April 23, p 1775–84),1 in which they analyse the current status of the 35 malaria-eliminating countries including China, indicating the feasibility and challenges of global malaria eradication. Because of the drastic decrease of malaria morbidity between 2006–09, the Ministry of Health in China issued the Chinese Malaria Elimination Action Plan (2010–2020). 2 In this ambitious plan, the goal of malaria elimination in China will be achieved by 2020 (ie, no indigenous cases by 2017). Malaria elimination in China is already getting closer, with only 56 indigenous cases reported in 2014, compared to over 24 million cases in the early 1970s.2,3 Malaria importation remains the most serious challenge, because imported cases might cause resurgence in susceptible areas. The proportion of imported malaria cases in China has increased persistently from 1676 (7%) of 24088 malaria cases in 2000, to 3021 (98%) of 3077 cases in 2014. 3,4 Africa and southeast Asia are the predominant sources of imported malaria to China. In 2011 and 2012 for example, 50·24% of imported cases in China were from Africa, and 42·42% from southeast Asia. Only a few countries in these two highly endemic regions are expected to eliminate malaria by 2020,1 therefore China must prioritise its strategy of surveillance and response to centre on malaria cases with mobile and migrant populations in the process of elimination. China has accumulated great experience in malaria control, which are worth sharing with other endemic countries. In Asia, China takes joint actions with other countries in the Greater www.thelancet.com Vol 388 September 3, 2016
Mekong Subregion to containing and eliminating Plasmodium falciparum resistance to artemisinin, and has an active role in the networks including the Asia Pacific Malaria Elimination Network and Asia Pacific Leaders Malaria Alliance. 1 Malaria control in Africa also ranks a top priority in health cooperation between China and Africa.5 China has a responsibility to aid the control and elimination of malaria in other endemic countries, which in turn will consolidate the achievement of malaria elimination in China and contribute to global malaria eradication. We declare no competing interests.
Jin Chen, *Ning Xiao [email protected] National Institute of Parasitic Diseases, Chinese Center for Disease Control and Prevention, Shanghai, China; Key Laboratory of Parasite and Vector Biology, Ministry of Health, Shanghai, China; National Center for International Research on Tropical Diseases, Shanghai, China; and WHO Collaborating Centre for Tropical Diseases, Shanghai 200025, China 1
2
3
4
5
Newby G, Bennett A, Larson E, et, al. The path to eradication: a progress report on the malaria-eliminating countries. Lancet 2016; 387: 1775–84. Ministry of Health in China. Chinese malaria elimination action plan (2010–2020). http://www.nhfpc.gov.cn/jkj/s5873/201005/ f84f1c4b0f32420990d23b65a88e2d87.shtml (accessed April 25, 2016). Zhang L, Zhou SS, Feng J, Fang W, Xia ZG. Malaria situation in the People’s Republic of China in 2014. Zhongguo Ji Sheng Chon Xue Yu Ji Sheng Chong Bing Za Zhi 2015; 33: 319–26 (in Chinese). Feng J, Xia ZG, Vong S, Yang WZ, Zhou SS, Xiao N. Preparedness for malaria resurgence in China: case study on imported cases in 2000–2012. Adv Parasitol 2014; 86: 231–65. National Institute of Parasitic Diseases, Chinese Center for Disease Control and Prevention. The launching of China-UKTanzania collaborative pilot project on malaria control. http://en.ipd.org.cn:8080/en/ content/launching-china-uk-tanzaniacollaborative-pilot-project-malaria-control (accessed April 25, 2016).
Authors’ reply We thank Jin Chen and Ning Xiao for their Correspondence highlighting the exciting progress China has made toward achieving malaria elimination. As they mention, the drastic reduction in cases over the past few decades to just 56 in 2014 is remarkable and inspiring. The enabling factors for
elimination that we feature in our Review 1—including national-level political and financial commitment, ongoing collaboration with malariaendemic neighbours through regional initiatives, and rigorous surveillance and response activities—are all very well represented in China, and have certainly contributed to their recent success. In addition, China’s leadership within the region and in Africa is to be commended and used as a model for other countries approaching elimination. We would also like to highlight a new trilateral collaboration in the Asia-Pacific regoin between China (an elimination leader), Australia (a major donor), and Papua New Guinea (a high-transmission country), dedicated to improving malaria diagnosis within Papua New Guinea.2 This collaboration underscores the regional health security agenda which is driving investments in support of the regional goal of a malaria-free Asia Pacific by 2030. Chen and Xiao bring up an important point regarding the threat of importation. While much of the discussion in our Review centred on the risk of imported cases from endemic neighbouring countries, mitigated by cross-border coordination and regional data-sharing, another large source of imported cases is overseas employment. In addition to a robust surveillance system, such as China’s 1–3–7 approach 3 which has recently been implemented in other Asia-Pacific countries such as Thailand, rapid response to cases of malaria in returning overseas workers may involve passenger screening at ports of entry and engagement of private sector employers to establish a plan for diagnosis, treatment, and reporting of malaria in their workforce. Managing the risk of importation is a serious challenge that Sri Lanka is also currently facing,4 and critical factors for their success are strong collaboration and regular communication with organisations such as the military,
Dr Gopal Murti/Science Photo Library
Chinese action towards global malaria eradication
959
Correspondence
port administrators, religious groups, and the International Organization for Migration. Lessons such as these from countries that have recently achieved elimination or, like China, are on the verge of success, must be shared widely so that malaria programmes can learn from others’ experiences and continue to strengthen national and regional efforts. We declare no competing interests.
*Gretchen Newby, Erika Larson, Rima Shretta, Adam Bennett, Allison A Phillips [email protected] Global Health Group, University of California, San Francisco, San Francisco, CA, USA 1
2
3
4
Newby G, Bennett A, Larson E, et al. The path to eradication: a progress report on the malaria-eliminating countries. Lancet 2016; 387: 1775–84. Bishop J. Australia, China and PNG working together to tackle malaria. Government of Australia Department of Foreign Affairs and Trade, 2015. http://foreignminister.gov.au/ releases/Pages/2015/jb_mr_151108.aspx?w=t b1CaGpkPX%2FlS0K%2Bg9ZKEg%3D%3D (accessed June 14, 2016). Cao J, Sturrock HJW, Cotter C, et al. Communicating and monitoring surveillance and response activities for malaria elimination: China’s “1-3-7” strategy. PLoS Med 2014; 11: e1001642. Dharmawardena P, Premaratne RG, Gunasekera WM, Hewawitarane M, Mendis K, Fernando D. Characterization of imported malaria, the largest threat to sustained malaria elimination from Sri Lanka. Malar J 2015; 14: 177.
Treating sickle cell anaemia: the TWiTCH trial The TWiTCH trial (Feb 13, p 661)1 is the first randomised trial comparing hydroxyurea with transfusions in children with sickle cell anaemia with abnormal high transcranial doppler (TCD) flow velocities. We congratulate the authors for this important work. Nevertheless, we have some concerns about their conclusion. The authors conclude non-inferiority of hydroxyurea to transfusions; however, this might have been observed because of the following study design factors. An intentionto-treat analysis was used that would 960
predictably favour the hydroxyurea group (anti-conservative) when used with a non-inferiority model.2,3 A 24-month mean time-averaged TCD velocity estimation from a general linear mixed model using all TCD velocities captured throughout the trial was used, including velocities when patients were transfused during the 6–9–month overlap, or when rescue transfusions were used in case of low hydroxyurea response, which occurred in at least 32% of the patients. Also, patients had a mean age of 9·7 years at enrolment and long duration of past transfusions (4·5 years in the hydroxyurea group), so most patients might have not have been at risk at the time of enrolment. In our opinion, the follow-up period of the TWiTCH study was too short to conclude that hydroxyurea can substitute for chronic transfusions. The post-STOP2 trial4 reported strokes in several patients following reversion. Moreover, in the Créteil cohort, we have experience of hydroxyurea use in patients with normalised velocities and no stenosis. 5 Reversion to abnormal TCD was observed in 28% of patients, even on maximum tolerated dose, before the age of 9·5 years.6 Thus, the switch from transfusions to hydroxyurea in patients with history of abnormal TCD in countries where transfusions are available should be done with caution, with strict quarterly TCD control and transfusion reintroduction after reversion. We declare no competing interests.
*Françoise Bernaudin, Suzanne Verlhac, Sylvie Chevret [email protected] Department of Pediatrics (FB), and Medical Imaging Department (SV), Referral Center for Sickle Cell Disease, CHIC Hospital, Paris XII University, Créteil, France; and Biostatistics and Clinical Epidemiology, Center of Research on Epidemiology and Biostatistics Sorbonne Paris Cité, Paris Diderot University, Saint Louis, Paris, France (SC) 1
Ware RE, Davis BR, Schultz WH, et al. Hydroxycarbamide versus chronic transfusion for maintenance of transcranial doppler flow velocities in children with sickle cell anaemia–TCD With Transfusions Changing to Hydroxyurea (TWiTCH): a multicentre, open-label, phase 3, non-inferiority trial. Lancet 2016; 387: 661–70.
2
3
4
5
6
Rohmel J. Therapeutic equivalence investigations: statistical considerations. Stat Med 1998; 17: 1703–14. Matsuyama Y. A comparison of the results of intent-to-treat, per-protocol, and g-estimation in the presence of non-random treatment changes in a time-to-event non-inferiority trial. Stat Med 2010; 29: 2107–16. Lee MT, Piomelli S, Granger S, et al. Stroke Prevention Trial in Sickle Cell Anemia (STOP): extended follow-up and final results. Blood 2006; 108: 847–52. Bernaudin F, Verlhac S, Arnaud C, et al. Impact of early transcranial Doppler screening and intensive therapy on cerebral vasculopathy outcome in a newborn sickle cell anemia cohort. Blood 2011; 117: 1130–40. Bernaudin F, Verlhac S, Arnaud C, et al. Long-term treatment follow-up of children with sickle cell disease monitored with abnormal transcranial Doppler velocities. Blood 2016; 127: 1814–22.
We read with interest the results of the TWiTCH trial1 comparing hydroxyurea with transfusions for the treatment of sickle cell disease. As a patient-support charity, we acknowledge the potential of this study to inform and change clinical practice geared towards reducing the risk of childhood stroke associated with sickle cell disease. As strong advocates for patient’s choice, we believe informed choice should remain key to the use and interpretation of this research in clinical practice. Information such as known risk, the long-term effects of all treatment options, and the limitations of the research should be made available to patients in plain English, so that patients are equipped with the information they need to make credible, considered, and informed choices for their own unique circumstances. This study is missing a crucial element— the patient’s perspective should be given equal weight in view of the interpretation and strong conclusions. Our major concern with this study is risk. The TWiTCH study had a 1–2 year treatment period with extensive monitoring under trial conditions when the period of greatest risk after abnormal transcranial doppler (TCD) flow velocity diagnosis remains unknown and might be greater if the transfusion period is short. We need registry data to monitor patients with www.thelancet.com Vol 388 September 3, 2016
To coincide with World Malaria Day, The Lancet published a Review by Gretchen Newby and colleagues (April 23, p 1775–84),1 in which they analyse the current status of the 35 malaria-eliminating countries including China, indicating the feasibility and challenges of global malaria eradication. Because of the drastic decrease of malaria morbidity between 2006–09, the Ministry of Health in China issued the Chinese Malaria Elimination Action Plan (2010–2020). 2 In this ambitious plan, the goal of malaria elimination in China will be achieved by 2020 (ie, no indigenous cases by 2017). Malaria elimination in China is already getting closer, with only 56 indigenous cases reported in 2014, compared to over 24 million cases in the early 1970s.2,3 Malaria importation remains the most serious challenge, because imported cases might cause resurgence in susceptible areas. The proportion of imported malaria cases in China has increased persistently from 1676 (7%) of 24088 malaria cases in 2000, to 3021 (98%) of 3077 cases in 2014. 3,4 Africa and southeast Asia are the predominant sources of imported malaria to China. In 2011 and 2012 for example, 50·24% of imported cases in China were from Africa, and 42·42% from southeast Asia. Only a few countries in these two highly endemic regions are expected to eliminate malaria by 2020,1 therefore China must prioritise its strategy of surveillance and response to centre on malaria cases with mobile and migrant populations in the process of elimination. China has accumulated great experience in malaria control, which are worth sharing with other endemic countries. In Asia, China takes joint actions with other countries in the Greater www.thelancet.com Vol 388 September 3, 2016
Mekong Subregion to containing and eliminating Plasmodium falciparum resistance to artemisinin, and has an active role in the networks including the Asia Pacific Malaria Elimination Network and Asia Pacific Leaders Malaria Alliance. 1 Malaria control in Africa also ranks a top priority in health cooperation between China and Africa.5 China has a responsibility to aid the control and elimination of malaria in other endemic countries, which in turn will consolidate the achievement of malaria elimination in China and contribute to global malaria eradication. We declare no competing interests.
Jin Chen, *Ning Xiao [email protected] National Institute of Parasitic Diseases, Chinese Center for Disease Control and Prevention, Shanghai, China; Key Laboratory of Parasite and Vector Biology, Ministry of Health, Shanghai, China; National Center for International Research on Tropical Diseases, Shanghai, China; and WHO Collaborating Centre for Tropical Diseases, Shanghai 200025, China 1
2
3
4
5
Newby G, Bennett A, Larson E, et, al. The path to eradication: a progress report on the malaria-eliminating countries. Lancet 2016; 387: 1775–84. Ministry of Health in China. Chinese malaria elimination action plan (2010–2020). http://www.nhfpc.gov.cn/jkj/s5873/201005/ f84f1c4b0f32420990d23b65a88e2d87.shtml (accessed April 25, 2016). Zhang L, Zhou SS, Feng J, Fang W, Xia ZG. Malaria situation in the People’s Republic of China in 2014. Zhongguo Ji Sheng Chon Xue Yu Ji Sheng Chong Bing Za Zhi 2015; 33: 319–26 (in Chinese). Feng J, Xia ZG, Vong S, Yang WZ, Zhou SS, Xiao N. Preparedness for malaria resurgence in China: case study on imported cases in 2000–2012. Adv Parasitol 2014; 86: 231–65. National Institute of Parasitic Diseases, Chinese Center for Disease Control and Prevention. The launching of China-UKTanzania collaborative pilot project on malaria control. http://en.ipd.org.cn:8080/en/ content/launching-china-uk-tanzaniacollaborative-pilot-project-malaria-control (accessed April 25, 2016).
Authors’ reply We thank Jin Chen and Ning Xiao for their Correspondence highlighting the exciting progress China has made toward achieving malaria elimination. As they mention, the drastic reduction in cases over the past few decades to just 56 in 2014 is remarkable and inspiring. The enabling factors for
elimination that we feature in our Review 1—including national-level political and financial commitment, ongoing collaboration with malariaendemic neighbours through regional initiatives, and rigorous surveillance and response activities—are all very well represented in China, and have certainly contributed to their recent success. In addition, China’s leadership within the region and in Africa is to be commended and used as a model for other countries approaching elimination. We would also like to highlight a new trilateral collaboration in the Asia-Pacific regoin between China (an elimination leader), Australia (a major donor), and Papua New Guinea (a high-transmission country), dedicated to improving malaria diagnosis within Papua New Guinea.2 This collaboration underscores the regional health security agenda which is driving investments in support of the regional goal of a malaria-free Asia Pacific by 2030. Chen and Xiao bring up an important point regarding the threat of importation. While much of the discussion in our Review centred on the risk of imported cases from endemic neighbouring countries, mitigated by cross-border coordination and regional data-sharing, another large source of imported cases is overseas employment. In addition to a robust surveillance system, such as China’s 1–3–7 approach 3 which has recently been implemented in other Asia-Pacific countries such as Thailand, rapid response to cases of malaria in returning overseas workers may involve passenger screening at ports of entry and engagement of private sector employers to establish a plan for diagnosis, treatment, and reporting of malaria in their workforce. Managing the risk of importation is a serious challenge that Sri Lanka is also currently facing,4 and critical factors for their success are strong collaboration and regular communication with organisations such as the military,
Dr Gopal Murti/Science Photo Library
Chinese action towards global malaria eradication
959
Correspondence
port administrators, religious groups, and the International Organization for Migration. Lessons such as these from countries that have recently achieved elimination or, like China, are on the verge of success, must be shared widely so that malaria programmes can learn from others’ experiences and continue to strengthen national and regional efforts. We declare no competing interests.
*Gretchen Newby, Erika Larson, Rima Shretta, Adam Bennett, Allison A Phillips [email protected] Global Health Group, University of California, San Francisco, San Francisco, CA, USA 1
2
3
4
Newby G, Bennett A, Larson E, et al. The path to eradication: a progress report on the malaria-eliminating countries. Lancet 2016; 387: 1775–84. Bishop J. Australia, China and PNG working together to tackle malaria. Government of Australia Department of Foreign Affairs and Trade, 2015. http://foreignminister.gov.au/ releases/Pages/2015/jb_mr_151108.aspx?w=t b1CaGpkPX%2FlS0K%2Bg9ZKEg%3D%3D (accessed June 14, 2016). Cao J, Sturrock HJW, Cotter C, et al. Communicating and monitoring surveillance and response activities for malaria elimination: China’s “1-3-7” strategy. PLoS Med 2014; 11: e1001642. Dharmawardena P, Premaratne RG, Gunasekera WM, Hewawitarane M, Mendis K, Fernando D. Characterization of imported malaria, the largest threat to sustained malaria elimination from Sri Lanka. Malar J 2015; 14: 177.
Treating sickle cell anaemia: the TWiTCH trial The TWiTCH trial (Feb 13, p 661)1 is the first randomised trial comparing hydroxyurea with transfusions in children with sickle cell anaemia with abnormal high transcranial doppler (TCD) flow velocities. We congratulate the authors for this important work. Nevertheless, we have some concerns about their conclusion. The authors conclude non-inferiority of hydroxyurea to transfusions; however, this might have been observed because of the following study design factors. An intentionto-treat analysis was used that would 960
predictably favour the hydroxyurea group (anti-conservative) when used with a non-inferiority model.2,3 A 24-month mean time-averaged TCD velocity estimation from a general linear mixed model using all TCD velocities captured throughout the trial was used, including velocities when patients were transfused during the 6–9–month overlap, or when rescue transfusions were used in case of low hydroxyurea response, which occurred in at least 32% of the patients. Also, patients had a mean age of 9·7 years at enrolment and long duration of past transfusions (4·5 years in the hydroxyurea group), so most patients might have not have been at risk at the time of enrolment. In our opinion, the follow-up period of the TWiTCH study was too short to conclude that hydroxyurea can substitute for chronic transfusions. The post-STOP2 trial4 reported strokes in several patients following reversion. Moreover, in the Créteil cohort, we have experience of hydroxyurea use in patients with normalised velocities and no stenosis. 5 Reversion to abnormal TCD was observed in 28% of patients, even on maximum tolerated dose, before the age of 9·5 years.6 Thus, the switch from transfusions to hydroxyurea in patients with history of abnormal TCD in countries where transfusions are available should be done with caution, with strict quarterly TCD control and transfusion reintroduction after reversion. We declare no competing interests.
*Françoise Bernaudin, Suzanne Verlhac, Sylvie Chevret [email protected] Department of Pediatrics (FB), and Medical Imaging Department (SV), Referral Center for Sickle Cell Disease, CHIC Hospital, Paris XII University, Créteil, France; and Biostatistics and Clinical Epidemiology, Center of Research on Epidemiology and Biostatistics Sorbonne Paris Cité, Paris Diderot University, Saint Louis, Paris, France (SC) 1
Ware RE, Davis BR, Schultz WH, et al. Hydroxycarbamide versus chronic transfusion for maintenance of transcranial doppler flow velocities in children with sickle cell anaemia–TCD With Transfusions Changing to Hydroxyurea (TWiTCH): a multicentre, open-label, phase 3, non-inferiority trial. Lancet 2016; 387: 661–70.
2
3
4
5
6
Rohmel J. Therapeutic equivalence investigations: statistical considerations. Stat Med 1998; 17: 1703–14. Matsuyama Y. A comparison of the results of intent-to-treat, per-protocol, and g-estimation in the presence of non-random treatment changes in a time-to-event non-inferiority trial. Stat Med 2010; 29: 2107–16. Lee MT, Piomelli S, Granger S, et al. Stroke Prevention Trial in Sickle Cell Anemia (STOP): extended follow-up and final results. Blood 2006; 108: 847–52. Bernaudin F, Verlhac S, Arnaud C, et al. Impact of early transcranial Doppler screening and intensive therapy on cerebral vasculopathy outcome in a newborn sickle cell anemia cohort. Blood 2011; 117: 1130–40. Bernaudin F, Verlhac S, Arnaud C, et al. Long-term treatment follow-up of children with sickle cell disease monitored with abnormal transcranial Doppler velocities. Blood 2016; 127: 1814–22.
We read with interest the results of the TWiTCH trial1 comparing hydroxyurea with transfusions for the treatment of sickle cell disease. As a patient-support charity, we acknowledge the potential of this study to inform and change clinical practice geared towards reducing the risk of childhood stroke associated with sickle cell disease. As strong advocates for patient’s choice, we believe informed choice should remain key to the use and interpretation of this research in clinical practice. Information such as known risk, the long-term effects of all treatment options, and the limitations of the research should be made available to patients in plain English, so that patients are equipped with the information they need to make credible, considered, and informed choices for their own unique circumstances. This study is missing a crucial element— the patient’s perspective should be given equal weight in view of the interpretation and strong conclusions. Our major concern with this study is risk. The TWiTCH study had a 1–2 year treatment period with extensive monitoring under trial conditions when the period of greatest risk after abnormal transcranial doppler (TCD) flow velocity diagnosis remains unknown and might be greater if the transfusion period is short. We need registry data to monitor patients with www.thelancet.com Vol 388 September 3, 2016